Abstract 839: HER2 expression occurs early in breast cancer dissemination

Abstract

Abstract Background: Systemic spread of disseminated tumor cells from the primary site may occur early in breast tumorigenesis. The role of HER2 in breast cancer (BC) dissemination is not well understood. We evaluated the expression of HER2 on peripheral blood Circulating Tumor Cells (CTCs) from women with various stages of breast cancer (BC). Methods: 81 women with preinvasive breast lesions (Atypical Ductal Hyperplasia, Lobular Carcinoma In Situ and Ductal Carcinoma In Situ), 101 women with early invasive BC and 35 women with metastatic BC were included. CTCs were defined as Cytokeratin 8,18,19+/CD45-/DAPI+ cells detected using the CellSearch® technology. Any staining for HER2 on CTCs using the CellSearch® HER2 profiling kit was considered positive. HER2 detection was calibrated through peripheral blood spiking experiments with MCF7 and SKBR3 cells. Results: > 1 CTCs/22.5mL of blood were detected in 6 of 81 (7%) women with preinvasive breast lesions (range 0-3 CTCs) and 15 of 101 (15%) women with early invasive BC (range 0-8 CTCs), whereas > 1 CTCs/7.5mL of blood were detected in 17 of 35 (49%) women with metastatic BC (range 0-1160 CTCs) (p<0.001). HER2 expression on CTCs was not associated with estrogen receptor (ER) and progesterone receptor (PR) expression or the histological grade of the primary tumor. In women with detectable CTCs, the ratio of HER2-positive CTCs/total CTCs was higher in HER2-positive than HER2-negative primary tumors (p=0.023). Despite a higher detection rate of CTCs, the ratio of HER2-positive CTCs/total CTCs was lower in metastatic BC (median 0.15, range 0-1.0) than in preinvasive (median 1.0, range 0-1.0) or early invasive BC (median 1.0, range 0.3-1.0) (p<0.001). Similar results were observed when only HER2-negative primary tumors were considered (p=0.004). Conclusion: This is the first report showing that HER2-positive CTCs can be detected in women with preinvasive breast lesions, further supporting the hypothesis that dissemination occurs early in breast tumorigenesis. HER2 expression on CTCs is more commonly observed in earlier stages of breast cancer, suggesting that HER2 plays an important role in early dissemination. The EORTC 90091-10093 trial will test the hypothesis that trastuzumab can eliminate HER2-positive CTCs in patients with HER2-negative early breast cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 839.